Predictors of Youth-Onset Type 2 Diabetes: UAB Clinical Center

青年发病 2 型糖尿病的预测因子：UAB 临床中心

• 批准号: 10582927
• 负责人: Ambika Pallikunnath Ashraf
• 金额: $ 5.81万
• 依托单位: UNIVERSITY OF ALABAMA AT BIRMINGHAM
• 依托单位国家: 美国
• 财政年份: 2023
• 资助国家: 美国
• 起止时间: 2023-03-10 至 2029-01-31
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10582927
• 关键词: Accounting; Adipose tissue; Adult; Affect; African American population; Age; Alabama; American; Archives; Beta Cell; Body Composition; Body fat; Body mass index; Carbohydrates; Cell physiology; Child; Childhood; Chronic stress; Clinic; Collaborations; Data; Deposition; Diabetes Mellitus; Diet; Dietary Carbohydrates; Dietary Sugars; Dual-Energy X-Ray Absorptiometry; Effectiveness; Effectiveness of Interventions; Endocrinology; Environmental Risk Factor; Ethnic Origin; Etiology; Evaluation; Exhibits; Family; Family history of; Fasting; Fatty Liver; Fatty acid glycerol esters; Functional disorder; Future; Genes; Genetic; Genetic Materials; Genetic Polymorphism; Genetic Predisposition to Disease; Genotype; Glucose; Hepatic; Hispanic Americans; Impaired fasting glycaemia; Impairment; Individual; Insulin; Insulin Resistance; Intervention; Intervention Studies; Leg; Lipids; Liver; Longitudinal cohort study; Measures; Metabolic; Monitor; Morbid Obesity; Mutation; Non-Insulin-Dependent Diabetes Mellitus; Not Hispanic or Latino; OGTT; Obesity; Outcome Measure; Participant; Pediatric Hospitals; Peripheral; Phenotype; Physiological; Physiology; Plasma; Prediabetes syndrome; Predictive Factor; Pregnancy; Prevalence; Probability; Process; Proinsulin; Psychosocial Factor; Publishing; Race; Recording of previous events; Research; Risk; Risk Factors; SNP genotyping; Scanning; Single Nucleotide Polymorphism; Site; Starch; Technical Expertise; Testing; Tissue Expansion; Universities; Variant; Visit; Weight Gain; Youth; adverse childhood events; aged; clinical center; cohort; diabetes risk; ethnic disparity; glucose monitor; glucose tolerance; hospital care; impaired glucose tolerance; indexing; insulin sensitivity; intrauterine environment; metabolomics; minority children; obesity risk; pediatric patients; predictive modeling; progression risk; racial disparity; recruit; response; retention rate; sex; sugar

Minority youth are at elevated risk for type 2 diabetes (T2D) relative to non-Hispanic whites (NHW), with African-Americans (AA) and Hispanic-Americans (HA) showing the greatest increase in prevalence since 2000. Our overarching hypothesis is that underlying genetic differences in minority children interact with environmental factors in an adverse manner to increase risk for T2D. For example, the elevated beta-cell responsiveness and reduced hepatic insulin extraction exhibited by AA may increase risk for obesity and beta- cell dysfunction in the context of a diet high in sugar and processed starches. HA have both a genetic predisposition to fatty liver, due to a mutation in the carbohydrate-responsive PNPLA3 gene, and a genetic impairment in the ability to expand peripheral adipose tissue. In the context of weight gain and a high- sugar/processed carbohydrate diet, these genetic factors may increase risk for insulin resistance. The global purpose of RFA-DK-21-002 is to identify factors that predict conversion to T2D, and that disproportionately predispose minority youth to T2D. With our “University of Alabama at Birmingham (UAB) Clinical Center,” we propose to recruit, phenotype, and follow for 5 years 100 at-risk youth aged 8-16 yr without T2D at baseline comprised primarily of AA children with extreme obesity. Our team excels in assessment of insulin sensitivity and beta-cell function; assessment of body composition and body fat distribution; evaluation of the intrauterine environment; and conducting longitudinal cohort studies with high retention. Published data indicate that the greatest risk factors for pediatric T2D are extreme obesity (BMI z score > 2.5), impaired glucose tolerance (2-h glucose >140 mg/dL and <200 mg/dL), weight gain, and family or maternal/gestational history of diabetes. We will assess all of these variables with annual testing visits that will include an oral glucose tolerance test and dual-energy-X-ray absorptiometry (DXA) for body composition and fat distribution. In addition, we will collect genetic material for assessment of targeted SNPs with known association to T2D risk, and we will assess environmental factors such as psychosocial variables and diet. Sera/plasma will be archived for future metabolomics. Prediction models will be developed for incident T2D, as well as for prevalent and incident IGT, using suites of anthropometric/demographic, phenotypic, and genotypic variables. We hypothesize that ethnicity/race will not be statistically related to incident T2D when accounting for genotypic and/or phenotypic factors that affect risk for T2D, and their potential interaction with environmental factors. Results from this study will identify the genetic underpinnings of the phenotypic and anthropometric/familial factors that associate with, and reflect the pathophysiology of, IGT and T2D, and will determine whether these determinants differ with ethnicity/race. As such, the results of this study will identify targets for intervention, and markers for monitoring intervention effectiveness, that can be utilized in subsequent intervention studies.

与非西班牙裔白人(NHW)相比，少数族裔青年患2型糖尿病(T2D)的风险更高， 非洲裔美国人(AA)和西班牙裔美国人(HA)的患病率出现了自2000年以来的最大增幅。 我们的主要假设是，少数民族儿童潜在的遗传差异与 环境因素以不利的方式增加T2D的风险。例如，升高的β细胞 再生障碍性贫血表现出的反应性和肝脏胰岛素摄取减少可能会增加肥胖和β-糖尿病的风险。 在高糖和加工淀粉饮食的背景下，细胞功能障碍。HA既有基因，也有 由于碳水化合物反应性PNPLA3基因突变而易患脂肪肝，以及 扩张外周脂肪组织的能力受损。在体重增加和高- 糖/加工碳水化合物饮食，这些遗传因素可能会增加胰岛素抵抗的风险。《环球报》 RFA-DK-21-002的目的是确定预测转换为T2D的因素以及不成比例的因素 使少数族裔青年倾向于T2D。与我们的“阿拉巴马大学伯明翰分校(UAB)临床中心”合作 建议招募100名8-16岁无T2D的高危青年，并进行为期5年的跟踪调查 主要由患有极端肥胖症的AA儿童组成。我们的团队在胰岛素敏感性评估方面表现出色 和β细胞功能；身体成分和体脂分布的评估；宫内评估 以及进行高保留率的纵向队列研究。公布的数据表明， 儿童T2D的最大危险因素是极度肥胖(BMI z Score&gt；2.5)、糖耐量受损(2-h 血糖140 mg/dL和200 mg/dL)、体重增加，以及糖尿病家族史或母孕史。我们 将通过每年的检测访问来评估所有这些变量，其中将包括口服葡萄糖耐量测试和 身体成分和脂肪分布的双能X射线吸收测量仪(DXA)。此外，我们还将收取 用于评估已知与T2D风险相关的靶向SNPs的遗传物质，我们将评估 环境因素，如心理社会变量和饮食。血清/血浆将存档以备将来使用 代谢组学。将为事件T2D以及流行和事件IGT开发预测模型， 使用人体测量学/人口学、表型和遗传型变量组合。我们假设 当考虑到基因和/或表型时，种族/种族与事件T2D在统计上不相关 影响T2D风险的因素，以及它们与环境因素的潜在交互作用。由此产生的结果 研究将确定表型和人体测量/家族因素的遗传基础 与IGT和T2D相关并反映其病理生理学，并将确定这些 决定因素因族裔/种族而异。因此，这项研究的结果将确定干预目标， 和监测干预效果的标记物，可用于后续干预研究。